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Table 2 MSC-based protocols to generate beta cell-like cells

From: An overview on small molecule-induced differentiation of mesenchymal stem cells into beta cells for diabetic therapy

Source/type of MSC Method Endodermal differentiation Pancreatic or endocrine differentiation Maturation Genes analyzed Efficiency In vivo testing reported Functional analysis Protocol duration in days Reference
Umbilical cord Extracellular matrix NA 25.2 No 9 [64]
Umbilical cord Small molecule Nicotinamide in high glucose C-peptide No 7 [65]
Umbilical cord ECM + small molecule + GF High-glucose, retinoic acid, nicotinamide, EGF FBS and exendin-4 Insulin, glucagon, Glut-2, PDX1, PAX4, NGN3 25 No EM 15 [66]
Umbilical cord Small molecule + peptide High glucose, nicotinamide, exendin-4, 2-mercaptoethanol Insulin,PDX1, glucagon No Nil 7 [67]
Umbilical cord blood Plasmid electro transfer PDX1 plasmid electro transfer PDX1, Ngn3, NKX6.1 82.94 (PDX1 +ve cells) No Nil 10 [68]
Wharton jelly Small molecule + GF High glucose and RA, L-nicotinic acid and EGF FBS and exendin-4 PDX1, NGN3, Glut2, and insulin No Dithizone staining, c-pep quantification 14 [69]
Placenta Small molecule + peptide l-Taurine and BSA l-Taurine, nicotinamide, GLP-1, BSA Insulin, glucagon, somatostatin 65 Yes c-pep/insulin quantification, dithizone staining 20 [61]
Bone marrow Small molecule + peptide High glucose and nicotinamide Exendin-4 PDX1, NGN3, NKX6.1, PAX4, Glut 2, glucagon, insulin 43 Yes Dithizone staining, EM, c-pep quantification, calcium imaging 29 [70]
Bone marrow Small molecule + GF bFGF, high glucose, and nicotinamide Nicotinamide, Activin A, and exendin 4 NKX6.1, ISL-1, NEUROD 1, Glut2, Pax6, PDX1, NGN3, insulin and glucagon 38.9 Yes Dithizone staining, EM, c-pep quantification 15 [71]
Bone marrow Adenoviral transfection   Transfection using PDX1 or VEGF Insulin 50 Yes 2 [72]
Bone marrow Small molecule + peptide Nicotinamide and exendin-4 PDX1, NGN3, PAX4, IAPP, and insulin 20 Yes 5 [73]
Bone marrow Small molecule + GF BFGF, EGF Nicotinamide, Activin, Betacellulin PDX1, MAF-A,B, NGN3, PAX4, insulin, c-peptide 5 Yes EM 18 [74]
Bone marrow Viral transfection Lentiviral transfection of miR-375 and anti-miR-9. PDX1, NKX6., FoxA2, GCG, insulin, NGN3 85 No Dithizone staining, c-pep quantification 21 [75]
Urine Small molecules IDE1, vitamin C Indolactam V, retinoic acid Nicotinamide, DAPT, SB203580 Sox-17, FoxA2, PDX1, NKX6.1, insulin, c-peptide 80 No c-pep quantification 30 [76]
Dental Small molecules + peptide High glucose and retinoic acid Low glucose, nicotinamide, EGF, Exendin A, Activin A, indolactam V PDX1, NKx6.1, NGN3, Glut2, MAfA No c-pep quantification, dithizone staining 21 [77]
Adipose Small molecule + peptide Sodium butyrate and high glucose l-Taurin Nicotinamide and GLP-1 Hnf3β, TCF2, Sox17, PDX1, Ngn3, NeuroD, PAX4 No 16–18 [78]
Bone marrow Retroviral infection PDX1 infection and culturing in bFGF PDX1, NeuroD1, NGN3, NKX6.1, ISl1 40–70 Yes c-pep/insulin quantification 21 [72]
Bone marrow Adenoviral transfection PDX1 infection and culturing in GLP 1 NGN3, insulin, GK, Glut2, and glucagon Yes c-pep/insulin quantification, calcium imaging 14 [79]
Bone marrow Serum-free culture Serum-free media culture NGN3, Brn4, NKX6.1, PAX6, and Isl1 33 Yes c-pep quantification 6–7 [80]
  Serum free + small molecules + GF 1. High glucose and conophylline PDX1, insulin, glucagon ~ 2.5 for all protocols No Dithizone staining, c-peptide quantification 15 [81]
2. High glucose, trichostatin and GLP-1 10
3. High glucose and 2-ME, bFGF and EGF, betacellulin, nicotinamide, and activin 18
Bone marrow Adenoviral transfection Infection of IPF1, HLXB9, and FOXA2 PDX1, NEUROD1, NKX6.2, Pax 6 50 No 14 [82]
Adipose Small molecules + GF High glucose, nicotinamide, Exendin, HGF, pentagastrin, activin A Isl-1, Ipf-1, NGN, insulin, glucagon 10 Yes 3 [83]
  1. Merged boxes represent the pancreatic and maturation stages induced together. Efficiency was calculated as the percentage of insulin- or c-peptide-positive cells at the end of the differentiation. FBS fetal bovine serum, GF growth factors, bFGF basic fibroblast growth factor, EGF epidermal growth factor, VEGF vascular endothelial growth factor, HGF hepatocyte growth factor